Immune checkpoint inhibitors (ICPIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand PD-L1. ICPIs are now approved for the treatment of a wide array of malignancies, with rates of durable responses in the metastatic setting far exceeding what would be expected from conventional chemotherapy. ICPIs have also been associated with rare but serious immune-related adverse events due to over-activation of the immune system that can affect any organ, including the gastrointestinal tract and liver. As the use of ICPIs in oncology continues to increase, ICPI-associated colitis and hepatitis will be encountered frequently by gastroenterologists and hepatologists. This review will focus on the diagnosis and management of ICPI-associated colitis and hepatitis. We will also compare these ICPI-related toxicities with sporadic inflammatory bowel disease and autoimmune liver disease.